Respiratory infection with rhinovirus interferes with the induction of tolerance to aeroallergens (P6007)

Abstract

Abstract Respiratory viral infections can influence the course of asthma at different time points. Rhinovirus (RV) infections during early age associate with a higher frequency of asthma in later childhood. Because airway exposure to innocuous antigen normally engenders T cell tolerance and prevents the development of airway inflammation, we examined the effect of RV infection on airway tolerance induced by exposure to intranasal OVA. We found that simultaneous infection with RV1B, a minor serotype, that binds LDL receptors in mice, abrogated tolerance induced by exposure to OVA, suppressing the generation of antigen-specific CD4+forkhead box protein 3 (FOXP3)+ regulatory T (Treg) cells while at the same time promoting IL-4-secreting effector CD4+ T cells. Rhinovirus infection in-vivo resulted in selective lung expression of the innate cytokines thymic stromal lymphopoietin (TSLP) and IL-33, and the T cell costimulatory TNF family molecule OX40L that is regulated by TSLP. Furthermore, RV infection subsequently resulted in full susceptibility to develop asthmatic disease, which was blocked by targeting TSLPR, IL-33R, or OX40L. These results suggest that RV infection of the respiratory tract can prevent the induction of tolerance to inhaled antigen through a mechanism involving TSLP, IL-33 and OX40L that results in susceptibility to developing acute allergic lung inflammation.